Project Summary/Abstract: Overall This application seeks to renew the University of Kentucky Alzheimer?s Disease Core Center (UK-ADC), an experienced and collaborative ADC originally funded in 1985. Our principal mission is to serve as the focal point for all AD-related activities at UK and this region of the United States, by providing an environment and core resources that catalyze innovative research, outreach, education, and clinical programs. Our signature resources include: 1) a cognitively normal group of ~500 subjects followed longitudinally, with all committed to brain autopsy upon death; 2) a strong program in clinical-neuropathological correlations and short postmortem interval autopsies; 3) a maturing program studying the early preclinical biological emergence of pathology that may lead to dementia states, with an increasing focus on antemortem imaging and CSF biomarker collection; 4) an integrated centralized database and innovative biostatistical expertise to characterize clinical and biological transitions; and 5) a successful and close partnership with the African-American community and increased participation of underrepresented individuals in our longitudinal cohort and ADC-affiliated research studies and clinical trials. The overall scientific emphasis of the UK-ADC continues to be on our interrelated themes: Transitions & Translation. Our well-characterized, longitudinal cohort and historically strong neuropathology program focused on normal aging, preclinical disease states and early cognitive transitions have been central to our success in defining early pathogenic mechanisms underlying the transitions from normal cognitive aging to impairment. The depth of expertise and collaborative nature of our investigators have also resulted in substantial progress on translation of that knowledge into new targets and novel therapeutic strategies. The UK-ADC will continue to provide the infrastructure and resources to focus on these integrated themes and advance innovative AD research through the pursuit of four overarching specific aims. Aim 1. Facilitate and enhance basic, translational and clinical research in AD and related dementias. Aim 2. Provide the necessary resources and interactive environment to support and create new opportunities for innovative research. Aim 3. Maintain and grow educational opportunities and community partnerships to promote awareness, increase participation in research, and provide an innovative and interdisciplinary training environment. Aim 4. Contribute to the national efforts to advance AD research, education, and care. The UK-ADC provides an infrastructure and environment that focuses on these integrated themes and advances AD research, education, outreach, and clinical programs through six highly interactive and effective components: Administrative Core, Clinical Core, Data Management and Statistics Core, Neuropathology Core, Outreach and Recruitment Core, and Research Education Component.